Objectives: Recent animal studies have shown that intravenous fat emulsion (IFE) increases survival and hemodynamics in severe verapamil toxicity. However, the optimal dose of IFE is unknown. The primary objective was to determine the optimal dose of IFE based on survival in severe verapamil toxicity. Secondary objectives were to determine the effects on hemodynamic and metabolic parameters. The hypothesis was that there is a dose-dependent effect of IFE on survival until a maximum dose is reached.Methods: This was a controlled dose-escalation study. Thirty male rats were anesthetized, ventilated, and instrumented to record mean arterial pressure (MAP) and heart rate (HR). Verapamil toxicity was achieved by a constant infusion of 15 mg ⁄ kg ⁄ hr. After 5 minutes, a bolus of 20% IFE was given. Animals were divided into six groups based on differing doses of IFE. Arterial base excess (ABE) was measured every 30 minutes. Data were analyzed with analysis of variance.
Results:The mean survival time for each dose of IFE was 0 mL ⁄ kg = 34 minutes, 6.2 mL ⁄ kg = 58 minutes, 12.4 mL ⁄ kg = 63 minutes, 18.6 mL ⁄ kg = 143.8 minutes, 24.8 mL ⁄ kg = 125.6 minutes, and 37.6 mL ⁄ kg = 130 minutes. Post hoc testing determined that the 18.6 mL ⁄ kg dose resulted in the greatest survival when compared to other doses. It increased survival 107.2 minutes (p = 0.004), 91.2 minutes (p = 0.001), and 80.8 minutes (p = 0.023) when compared to the lower doses of 0, 6.2, and 12.4 mL ⁄ kg, respectively. There was no added benefit to survival for doses greater than 18.6 mL ⁄ kg. The secondary outcomes of HR, MAP, and ABE showed the most benefit with 24.8 mL ⁄ kg of IFE at both 30 and 60 minutes.
Conclusions:The greatest benefit to survival occurs with 18.6 mL ⁄ kg IFE, while the greatest benefit to HR, MAP, and BE occurs at 24.8 mL ⁄ kg IFE. The optimal dose for the treatment of severe verapamil toxicity in this murine model was 18.6 mL ⁄ kg.
Objectives: L-Carnitine is an essential compound involved in cellular energy production through free fatty acid metabolism. It has been theorized that severe verapamil toxicity ''shifts'' heart energy production away from free fatty acids and toward other sources, contributing to profound cardiogenic shock. The primary study objective was to determine whether intravenous (IV) L-carnitine affects survival in severe verapamil toxicity. Secondary objectives were to determine the effects on hemodynamic parameters. The authors hypothesized that IV L-carnitine would increase both survival and hemodynamic parameters in severe verapamil toxicity.Methods: This was a controlled, blinded animal investigation. Sixteen male rats were anesthetized, ventilated, and instrumented to record mean arterial pressure (MAP) and heart rate. Verapamil toxicity was achieved by a constant infusion of 5 mg ⁄ kg ⁄ hr. After 5 minutes a bolus of 50 mg ⁄ kg of either L-carnitine or normal saline was given. The experiment concluded when either 10% of baseline MAP was achieved or 150 minutes had elapsed. The data were analyzed using Kaplan-Meier analysis, log rank test, and analysis of variance. Conclusions: When compared with saline, IV L-carnitine increases survival and MAP in a murine model of severe verapamil toxicity.
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